This proposal will evaluate the immunoregulation that develops during adoptively transferred or actively induced Experimental Allergic Encephalomyelitis (EAE). The analysis will involve donor contribution to the disease process, variables associated with the obligatory in vitro expansion of a transfer active cell population, and recipient participation in the development of paralytic EAE following cell transfer. The studies will define the activity and point(s) of control expressed by acquired or induced suppressor cells and will test the hypothesis that EAE effector cell activity is not controlled by the usual patterns of immunologic regulation. Planned experiments will also determine the relationship of the restriction imposed on cell interactions, as defined by the Major Histocompatibility Complex (MHC), to the restrictions observed in adoptive transfer of EAE. A similar analysis of MHC regulation in an autoimmune disease will be conducted with various inbred strains of rat as well as irradiation induced chimeras (employing the Brown-Norway (BN), Lewis (L) and LXBN F1 hybrid for chimera production). These latter studies of the chimera response will determine if actively induced disease, compared with adoptively transferred disease, is MHC restricted or if the initial requirements/restrictions for immune cell interaction are distinct from those MHC defined restrictions of target tissue destruction.